AAC Accepts, published online ahead of print on 26 October 2009

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Padilla, E. Articles by Albertí, S. PubMed PubMed Citation Articles by Padilla, E. Articles by Albertí, S.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother. doi:10.1128/AAC.00715-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence.

Emma Padilla, Enrique Llobet, Antonio Doménech-Sánchez, Luis Martínez-Martínez, José Antonio Bengoechea, and Sebastián Albertí^*

Institut Universitari dInvestigacions en Ciències de la Salut (IUNICS) and Departament de Biologia, Universitat de les Illes Balears (UIB), Palma de Mallorca, Spain; Fundación Caubet-CIMERA Illes Balears and Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Bunyola, Spain; Servicio de Microbiología, Hospital Universitario Marques de Valdecilla, and Departmento de Biología Molecular, Universidad de Cantabria, Santander, Spain; Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain

^* To whom correspondence should be addressed. Email: sebastian.alberti{at}uib.es.

Respiratory infections caused by Klebsiella pneumoniae are characterized by a high rate of mortality and morbidity. Management of these infections is often difficult, due to the high frequency of strains that are resistant to multiple antimicrobial agents. Multidrug efflux pumps play a major role as a mechanism of antimicrobial resistance in gram-negative pathogens. In the present study, we investigated the role of the K. pneumoniae AcrRAB operon in antimicrobial resistance and virulence by using isogenic knockouts deficient in the AcrB component and the AcrR repressor derived both from the virulent strain 52145R. We demonstrated that the AcrB knockout was not only more susceptible to quinolones but also to other antimicrobial agents, including -lactams, compared to the wild-type strain and the AcrR knockout. We further showed that the AcrB knockout was more susceptible to antimicrobial agents present in human bronchoalveolar lavage fluid and to human antimicrobial peptides than the wild-type strain and the AcrR knockout. Finally, the AcrB knockout exhibited a reduced capacity to cause pneumonia in a murine model in contrast to the wild-type strain. Results of this study suggest that, in addition to contribute to the multidrug resistance phenotype, the AcrAB efflux pump may represent a novel virulence factor required for K. pneumoniae to resist innate immune defence mechanisms of the lung hence facilitating the onset of pneumonia.